In vitro synergistic activity of ketoconazole with valproic acid against Candida species.

The susceptibility of 148 strains of Candida albicans and 20 strains of Candida species from patients was tested against ketoconazole (CAS 65277-42-1, KTZ), valproic acid (CAS 99-66-1, VPA) and the combination of KTZ and VPA, using Sabouraud's and YNB (yeast nitrogen base) media. Minimal inhibitory concentrations (MIC) with regard of C. albicans determined on diagnostic plates which contained Sabouraud's medium gave values of 49.84 +/- 5.83 mg/l (KTZ) and 202.97 +/- 17.70 mg/l (VPA), and on plates which contained YNB agar, values of 8.06 +/- 0.99 mg/l (KTZ) and 122.57 +/- 12.08 mg/l (VPA). The combination of KTZ and VPA in various ratios (1:1, 1:2, 2:1) was found to exert synergistic effects against C. albicans on Sabouraud's medium and the mean values of the combinations were: 4.29 +/- 0.37, 5.29 +/- 0.37, 5.02 +/- 0.38 mg/l. These results were significantly different (p < 0.001) compared with KTZ. The findings indicate that VPA, an antiepileptic drug, increases the antifungal activity of KTZ against C. albicans and Candida species in vitro.